Objective
Myelodysplastic Syndromes (MDS) form a group of blood cell disorders, with high risk for development of secondary Acute Myeloid Leukaemia. The number of patients are increasingly being treated with intensive anti-leukaemia therapy. Generally, the treatment effects are inferior to those obtained in primary leukaemia. European-wide clinical evaluation of this new treatment modality was started in 1993 within the framework of the EORTC and the EBMT.
In the present BIOMED 2 project the co-operating research groups carry out an in-depth study to elucidate the underlying molecular and genetic mechanisms of MDS-pathogenesis, and of MDS-treatment. Analysis of the nature of remission and monitoring of residual disease is thought to be essential for rational application of intensive, and expensive myelotoxic treatment of MDS or s-AML. Especially, the question is emphasised to which extent intensive chemotherapy or autologous stem cell transplantation induces cytogenetic and polyclonal remission. This knowledge will enable to predict impact of the treatment on the duration of polyclonal remission and on the prognosis of the patients. As a consequence an objective instrument will become available to support the clinical decision process leading to a treatment policy in which expected outcome for the patient is considered.
Qualitative Objectives Concern :
- Assessment of efficacy and effectiveness of intensive antileukaemic therapy (cytogenetic and clonal remission, clinical response, survival and costs)
- Standardisation and quality control of molecular techniques in malignant haematology, with special emphasis on Fluorescent In Situ Hybridisation (FISH) and Polymerase Chain Reaction (PCR).
- Promotion of vital links between basic research and clinical studies.
The study includes patients, already participating in a recently started European study. FISH and molecular analysis of blood and bone marrow samples will provide evaluation of monoclonal versus polyclonal remission. Cell populations of female MDS patients with and without the characteristic cytogenetic markers will be assessed for clonality by X-chromosome inactivation patterns. During the project period an intensive quality assessment programme is executed in order to assure high comparability of results obtained in different laboratories.
The project will provide knowledge concerning the molecular mechanisms of MDS. It will increase access to sophisticated laboratory techniques for a number of clinical institutes. Moreover, it will contribute to improvement of the medical decision process concerning alternative treatment strategies in malignant haematology, especially with regard to MDS.
Fields of science
Topic(s)
Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
6500 HB Nijmegen
Netherlands